Study of PF-05208756, Moroctocog Alfa (AF-CC), Xyntha For Male Chinese Subjects With Hemophilia A

NCT02461992 | Completed Phase 1 Results

• 2 other identifiers: B18310822015-003685-88
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

Brief Summary

An open-label, single dose pharmacokinetic study of Xyntha (Moroctocog Alfa (AF-CC), Recombinant Factor VIII) in male Chinese subjects with hemophilia A

Conditions

Hemophilia A

Keywords

FVIII activity

Outcome Measures

Primary Outcomes (10)

• Maximum Plasma FVIII Activity (Cmax)

  Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose

• Area Under the Plasma FVIII Activity-Time Profile From Time 0 to Time of the Last Quantifiable Concentration (AUClast)

  Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose

• Area Under the Plasma FVIII Activity-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf)

  Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose

• Time to Reach Maximum Observed Plasma Concentration (Tmax)

  Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose

• Clearance (CL)

  Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

  Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose

• Volume of Distribution at Steady-State (Vss)

  Volume of distribution is the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss is the volume of distribution at steady-state.

  Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose

• Terminal Phase Rate Constant (Kel)

  Terminal phase rate constant is the absolute value of the slope of a linear regression during the terminal phase of the natural--logarithm transformed concentration--time profile.

  Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose

• Terminal Elimination Half-Life (t1/2)

  Terminal half-life is the time measured for the plasma concentration to decrease by one half.

  Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose

• Mean Residence Time (MRT)

  MRT = AUMCinf / AUCinf, where AUMCinf is the area under the first moment curve from zero time to infinity calculated as AUMCinf = AUMCt + ((t x Ct) / kel) + (Ct / kel\^2). AUMCt is the area under the first moment curve from zero time to time t calculated using the trapezoidal method.

  Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose

• Incremental Recovery (INCREC)

  Incremental recovery is the increase in circulating FVIII activity for every IU of Xyntha administered per kilogram of body weight.

  Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose

Other Outcomes (4)

• Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)

  Baseline up to Day 28

• Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern

  Baseline up to Day 4

• Number of Participants With Potentially Clinically Significant Vital Signs Findings

  Baseline up to Day 4

Study Arms (1)

Intravenous infusion of Xyntha

EXPERIMENTAL

observation arm

Drug: Intravenous infusions of Xyntha

Interventions

Intravenous infusions of Xyntha DRUG

A single dose 50IU/kg dose of Xyntha administered by intravenous infusion within 10 minutes on Day 1

Intravenous infusion of Xyntha

Eligibility Criteria

• Age: 6 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male Chinese subjects 6 years or older (weight \>20 kg) with severe hemophilia A (factor VIII activity \<1%) previously treated with \> 150 exposure days to any FVIII-containing products.
• Subjects should not have received an infusion of any FVIII products for at least 3 days (at least 72 hours) before the administration of Xyntha on Day 1.
• Subjects must be in a non bleeding state before the administration of Xyntha on Day 1.
• Evidence of a personally or legally acceptable representative (legally acceptable representative is only applicable to pediatric subjects) signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
• Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

You may not qualify if:

• Subjects with any of the following characteristics/conditions will not be included in the study:
• Current FVIII inhibitor or history of FVIII inhibitor (defined as \> upper limit of normal (ULN) of the local reporting laboratory).
• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing) or clinical findings at Screening.
• Diagnosed with any other bleeding disorder in addition to hemophilia A.
• Documented Human Immunodeficiency Virus (HIV).
• Subjects anticipating elective surgery or other invasive procedure within 1 month following study entry.
• Treatment with immunomodulatory therapy within 30 days or 5 half lives whichever is longer, prior to study entry or planned use for the duration of study participation.
• Subjects with known hypersensitivity to the active substance or to any of the excipients of Xyntha.
• Subjects with a known hypersensitivity to Chinese Hamster Ovary cell (CHO cell) proteins.
• Subjects with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study specific laboratory and confirmed by a single repeat, if deemed necessary: significant hepatic or renal impairment (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3 x ULN, or total bilirubin \>2 x ULN or serum creatinine \>2 x ULN), prothrombin time \>1.5 x ULN, platelet count \<80,000 L. Subjects with Gilbert's disease may be enrolled.
• Unwilling or unable to follow the terms of the protocol.
• Any condition which may compromise the subject's ability to comply with and/or perform study related activities or that poses a clinical contraindication to study participation, in the opinion of the investigator or sponsor.
• A positive urine drug screen.
• History of regular alcohol consumption exceeding 14 drinks/week (1 drink = 5 ounces (150 mL) of wine, 12 ounces (360 mL) of beer, or 1.5 ounces (45 mL) of hard liquor) within 6 months of screening.
• Treatment with an investigational drug within 30 days or 5 half lives preceding Day 1, whichever is longer.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (2)

Phase I Unit, Clinical Pharmacology Research Center, Peking Union Medical College Hospital

Beijing, 100032, China

Location

Hematology Department,Beijing Children's Hospital, Capital Medical University

Beijing, 100045, China

Location

Related Publications (1)

• Liu H, Wu R, Hu P, Sun F, Xu L, Liang Y, Nepal S, Qu PR, Huard F, Korth-Bradley JM. An Open-label, Single-dose, Pharmacokinetic Study of Factor VIII Activity After Administration of Moroctocog Alfa (AF-CC) in Male Chinese Patients With Hemophilia A. Clin Ther. 2017 Jul;39(7):1313-1319. doi: 10.1016/j.clinthera.2017.05.344. Epub 2017 Jun 7.

  PMID: 28601434 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Hemophilia A

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: BASIC SCIENCE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2015
• First Posted: June 3, 2015
• Study Start: July 1, 2015
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: September 7, 2016
• Results First Posted: June 15, 2016

Record last verified: 2016-07

Locations

CN (2)